The acquired immunodeficiency syndrome (AIDS) caused by HIV-1 is the leading cause of death in Africa and the fourth leading cause of death worldwide. This IPCAVD is developing HIV/AIDS vaccines that use DNA for priming and MVA for boosting (DNA/MVA vaccine) as well as a simpler and ultimately easier to deploy form of these vaccines, the use of MVA for both priming and boosting (MVA/MVA vaccine). Both the DNA and MVA vaccines are mature products that use single vectors to express virus like particles (VLP).This IPCAVD seeks to build GM-CSF, an adjuvant, into these products for expression in cis. In preclinical studies, co-expression of GM-CSF has substantially enhanced protection. A central hypothesis for the IPCAVD is that GM-CSF improves protection by enhancing the mucosal presence of elicited T cell and Ab responses. Clade C HIV-1 which is endemic in southern Africa and parts of Asia accounts for about one half of the infections worldwide and >90% of the cases in India, a country with a rapidly spreading infection that has surpassed South Africa in its total number of cases. The vaccine development effort of this IPCAVD is focused on developing a clade C vaccine for India. Dr. Harriet Robinson, the program director, has effectively led the development of the vaccines in this IPCAVD during a long-term collaboration between her laboratory at the Emory Vaccine Center, Dr. Bernard Moss's laboratory at the NIAID and Dr. Tom Folks'group at the US Centers for Disease Control. In 2004, GeoVax Inc. of Atlanta GA licensed the technology for the vaccines and entered into an inter-institutional agreement between Emory, NIAID, and CDC for further development and commercialization of the vaccines. This IPCAVD has been submitted by GeoVax where Dr. Robinson plans to move in the spring of 2007 to work full time on the development and translation of the vaccines that she and her team have developed. This IPCAVD has 3 projects and 2 cores. Dr. Mark Keister of GeoVax (P.I.) with Dr. Robinson as co-P.I. (at GeoVax) will lead the project developing and manufacturing immunogens. Dr. Rama Amara (at Emory) will lead preclinical studies in the SIV251/rhesus macaque model. Dr. Mark Mulligan (at Emory) will lead the project on clinical trials (conducted through the HVTN) with Dr. Robinson as co-Pi (at GeoVax) overseeing the conduct of ancillary immunogenicity assays. Dr. Robinson (at GeoVax) will lead the administrative core. Dr. Pamela Kozlowski will lead a mucosal Ab core at Harvard University. Critical decisions will be supported by both Internal and External Advisory Committees. A strength of this IPCAVD is its leadership by a private/public/academic/industrial team with demonstrated ability to conduct a focused vaccine development program to bring promising products to clinical trials and commercialization.